Noor M. Gajraj

Pregabalin: Its Pharmacology and Use in Pain Management

Pregabalin is a new synthetic molecule and a structural derivative of the inhibitory neurotransmitter &ggr;-aminobutyric acid. It is an &agr;2-&dgr; (&agr;2-&dgr;) ligand that has analgesic, anticonvulsant, anxiolytic, and sleep-modulating activities. Pregabalin binds potently to the &agr;2-&dgr; subunit of calcium channels, resulting in a reduction in the release of several neurotransmitters, including glutamate, noradrenaline, serotonin, dopamine, and substance P. In this review, I will discuss the pharmacology of pregabalin and available efficacy studies in pain management. This review will focus on the advances in pregabalin pharmacology since my previous review in 2005.

Prevention of pain on injection of propofol: a comparison of lidocaine with alfentanil.

We undertook a randomized, placebo-controlled, double-blind study to compare the use of alfentanil 1 mg and lidocaine 40 mg for the reduction of pain during injection of propofol. Eighty-nine patients were randomly allocated to one of three groups: Group L, lidocaine 40 mg added to 180 mg propofol; Group A, alfentanil 1 mg 30 s prior to propofol; or Group P, placebo (normal saline). The incidence of pain in the placebo group was 67%. Both treatment groups had a significantly lower incidence of pain than the placebo group (P < 0.002). There was no significant difference in the incidence of pain between the groups receiving lidocaine or alfentanil (13% and 24%, respectively). There was no significant difference in the induction dose of propofol between the groups. Fifty-two percent of patients who experienced pain at induction had recall of that pain in the recovery room. Alfentanil 1 mg and lidocaine 40 mg are both effective in reducing pain during injection of propofol. (Anesth Analg 1996;82:469-71)

Effect of the Duration of Electrical Stimulation on the Analgesic Response in Patients with Low Back Pain

BACKGROUND Electrical stimulation of peripheral nerves produces acute analgesic effects. This randomized, sham-controlled, crossover study was designed to evaluate the effect of differing durations of electrical stimulation on the analgesic response to percutaneous electrical nerve stimulation in 75 consenting patients with low back pain. METHODS All patients received electrical stimulation for four different time intervals (0, 15, 30, and 45 min) in a random sequence over the course of an 11-week study period. All active percutaneous electrical nerve stimulation treatments were administered using alternating frequencies of 15 and 30 Hz three times per week for 2 consecutive weeks. The prestudy assessments included the health status survey short form questionnaire and 10-cm visual analog scale scores for pain, physical activity, and quality of sleep, with 0 being the best and 10 being the worst. The pain scoring was repeated 5-10 min after each 60-min study session and 24 h after the last treatment session with each of the four methods. The daily oral analgesic requirements were assessed during each of the four treatment blocks. At the end of each 2-week treatment block, the questionnaire was repeated. RESULTS Electrical stimulation using percutaneously placed needles produced short-term improvements in the visual analog scale pain, physical activity, and quality of sleep scores, and a reduction in the oral analgesic requirements. The 30-min and 45-min durations of electrical stimulation produced similar hypoalgesic effects (48+/-21% and 46+/-19%, respectively) and were significantly more effective than either 15 min (21+/-17%) or 0 min (10+/-11%). The 30- and 45-min treatments were also more effective in improving physical activity and sleep scores over the course of the 2-week treatment period. In contrast to the sham treatment (0 min), the health status survey short form revealed that electrical stimulation for 15 to 45 min three times per week for 2 weeks improved patient function. CONCLUSION The recommended duration of electrical stimulation with percutaneous electrical nerve stimulation therapy is 30 min.

The effect of stimulus frequency on the analgesic response to percutaneous electrical nerve stimulation in patients with chronic low back pain

UNLABELLED Low back pain (LBP) is one of the most common medical problems in our society. Increasingly, patients are turning to nonpharmacologic analgesic therapies such as percutaneous electrical nerve stimulation (PENS). We designed this sham-controlled study to compare the effect of three different frequencies of electrical stimulation on the analgesic response to PENS therapy. Sixty-eight consenting patients with LBP secondary to degenerative lumbar disc disease were treated with PENS therapy at 4 Hz, alternating 15 Hz and 30 Hz (15/30 Hz), and 100 Hz, as well as sham-PENS (0 Hz), according to a randomized, cross-over study design. Each treatment was administered for a period of 30 min three times per week for 2 wk. The pre- and posttreatment assessments included the health status survey short form and visual analog scales for pain, physical activity, and quality of sleep. After receiving all four treatments, patients completed a global assessment questionnaire. The sham-PENS treatments failed to produce changes in the degree of pain, physical activity, sleep quality, or daily intake of oral analgesic medications. In contrast, 4-Hz, 15/30-Hz, and 100-Hz stimulation all produced significant decreases in the severity of pain, increases in physical activity, improvements in the quality of sleep, and decreases in oral analgesic requirements (P < 0.01). Of the three frequencies, 15/30 Hz was the most effective in decreasing pain, increasing physical activity, and improving the quality of sleep (P < 0.05). In the global assessment, 40% of the patients reported that 15/30 Hz was the most desirable therapy, and it was also more effective in improving the patients sense of well-being. We conclude that the frequency of electrical stimulation is an important determinant of the analgesic response to PENS therapy. Alternating stimulation at 15-Hz and 30-Hz frequencies was more effective than either 4 Hz or 100 Hz in improving outcome measures in patients with LBP. IMPLICATIONS The frequency of electrical stimulation seems to be an important determinant of the analgesic efficacy of percutaneous electrical nerve stimulation. Mixed low- and high-frequency stimulation was more effective than either low or high frequencies alone in the treatment of patients with low back pain.

Eutectic mixture of local anesthetics (EMLA) cream.

he strong mechanical stimulus of transcutaneous needle insertion (e.g., intravenous cannulaT tion) elicits neural activity from 1) pressure-sensitive Ruffini endings, 2) movement-sensitive hair follicle receptors (Pacinian corpuscles) situated in the dermis, 3) mechanoreceptors innervated by single nerve endings, and 4) polymodal nociceptors situated close to the dermal-epidermal border. The cutaneous pain receptors are of two types-the AS type, consisting of fast, myelinated fibers, and the C type receptor, composed of slow, unmyelinated fibers. C fiber receptors are also present in the subcutaneous tissue and in the vascular walls. Local anesthetics act by blocking impulses from these receptors. When a needle is inserted through skin that has been infiltrated with local anesthetic, patients may feel needle movement but not pain, suggesting that pain on needle insertion originates from the deeper receptors (single nerve endings) and not the more superficial mechanoreceptors. Many attempts have been made to produce local analgesia and to allow painless venipuncture by the topical application of drugs. Topical 40% lidocaine or 20% benzocaine have been employed, but their use has been limited by concerns about local irritation, systemic toxicity, and inadequate analgesia (1). With the advent of eutectic mixture of local anesthetics (EMLA@; Astra Pharmaceutical Products Inc., Westborough, MA), effective topical analgesia of intact skin is now feasible without the need for subcutaneous injections or exposure to high concentrations of local anesthetics. In countries in which it has been available for some time, it is claimed that intravenous induction has gradually become the technique of choice for pediatric patients (Meusing AEE. Induction techniques. Society for Pediatric Anesthesia 6th Annual Meeting, New Orleans 1992). With the recent introduction of EMLA@ into the United States, it is appropriate to review its pharmacology, efficacy, clinical uses, side effects, and contraindications.

Screening for problematic prescription opioid use

The proper medicinal use of opioids, in light of their notorious history and current relation to social ills, continues to be debated and remains unclear in several areas of medicine. This article will review several areas and points of controversy related to screening for potential problematic opioid behavior in chronic nonmalignant pain patients. Controversy over the prescription of opioids for chronic nonmalignant pain continues, despite the growing acceptance of this practice. Indeed, past research supports the beneficial use of opioids for noncancer pain. Unfortunately, traditional definitions of abuse and dependence, with their emphasis on tolerance and withdrawal, are inappropriate for chronic pain patients prescribed opioids. The component of traditional definitions of abuse and dependence that appears most applicable to chronic pain patients centers on the criterion that the patient continue to take the drug (in this case, the opioid) despite negative and harmful effects or despite any decrease in pain level. Although clinical observations exist about risk factors for opioid misuse in chronic pain patients, there is limited research. Further, the area of prescreening for problematic drug behavior is in its infancy. However, researchers have begun to delve into this challenging area and the application of rigorous empirical research will bring us closer to identifying those patients at risk so that their pain is managed without destructive outcomes in other areas of their life.

Effects of Prophylactic Nalmefene on the Incidence of Morphine-related Side Effects in Patients Receiving Intravenous Patient-controlled Analgesia

BACKGROUND Opioid-related side effects associated with intravenous patient-controlled analgesia can be reduced by a low-dose naloxone infusion. The influence of nalmefene, a pure opioid antagonist with a longer duration of action, on opioid-related side effects has not been evaluated. This study was designed to determine the dose-response relation for nalmefene for the prevention of morphine-related side effects in patients receiving intravenous patient-controlled analgesia. METHODS One hundred twenty women undergoing lower abdominal surgery were enrolled in the study. General anesthesia was induced using thiopental and rocuronium and maintained with desflurane, nitrous oxide, and fentanyl or sufentanil. All patients received neostigmine and glycopyrrolate to reverse residual neuromuscular blockade. No prophylactic antiemetics were administered. At the end of surgery, patients were randomized to receive saline, 15 microg nalmefene, or 25 microg nalmefene intravenously. The need for antiemetic and antipruritic drugs and the total consumption of morphine during the 24-h study were recorded. The incidences of postoperative nausea, vomiting, pruritus, and pain were recorded 30 min after patients were admitted to the postanesthesia care unit. In addition, patient remembrance of these side effects was noted at 24 h after operation. RESULTS The need for antiemetic and antipruritic medications during the 24-h study period was significantly lower in the patients receiving nahmefene compared with those receiving placebo. However, the need to treat side effects was similar in the two nahmefene groups. Prophylactic administration of nalmefene reduced the patients remembrance of nausea and itching as assessed 24 h after operation. Although the total consumption of morphine during the 24-h study period was similar in the three groups, retrospectively patients who received nalmefene characterized their pain as less severe in the previous 24 h. CONCLUSION Compared with placebo, prophylactic administration of nalmefene significantly decreased the need for antiemetics and antipruritic medications in patients receiving intravenous patient-controlled analgesia with morphine.

Cyclooxygenase-2 Inhibitors

C yclooxygenase (COX) catalyzes the initial step of arachidonic acid metabolism and prostaglandin production. COX activity has been found to be associated with two distinct isoenzymes, COX-1 and COX-2. COX-1 was hypothesized to be involved in the maintenance of physiologic functions such as gastric protection and hemostasis, whereas COX-2 was thought to be involved in pathophysiologic processes such as inflammation, pain, and fever. This compelling hypothesis led to the development of the currently available selective COX-2 inhibitors celecoxib, rofecoxib, and valdecoxib. These drugs have analgesic efficacy comparable with that of conventional nonsteroidal antiinflammatory drugs (NSAIDs). In addition, they have no antiplatelet activity at therapeutic dosages and may be associated with reduced gastrointestinal (GI) side effects compared with conventional NSAIDs such as ibuprofen.

Role of the laryngeal mask airway in the immobile cervical spine

STUDY OBJECTIVE To determine whether the laryngeal mask airway has a useful role in the airway management of patients whose cervical spines are immobilized in a rigid cervical collar. DESIGN A randomized study comparing the difficulty, rapidity, and success rate of ventilating patients with immobilized cervical spines using a laryngeal mask airway and an endotracheal tube. SETTING Medical center surgical unit. PATIENTS Twenty-eight ASA physical status I and II women scheduled to undergo elective gynecologic surgery requiring general anesthesia. INTERVENTIONS Tracheas of all anesthetized patients were sequentially intubated with an endotracheal tube and had a laryngeal mask inserted in random order. MEASUREMENTS AND MAIN RESULTS Mouth opening was measured, and a Mallampati classification was made in each subject both with and without a rigid Philadelphia collar in situ. The view at laryngoscopy was recorded. The time taken to insert both devices to allow for satisfactory ventilation and the degree of difficulty encountered were determined. With a cervical collar in situ, mouth opening was reduced up to 60%. The Mallampati assessment and laryngoscopic view were shifted to one suggestive of a more difficult intubation. The time taken to ventilate these patients and the difficulties encountered were significantly less when using the laryngeal mask (p = 0.0001). A successful outcome was more likely following insertion of the laryngeal mask than when attempting intubation with an endotracheal tube. CONCLUSIONS The laryngeal mask airway compared favorably with an endotracheal tube in success rate, difficulty of insertion, and time to position correctly in this patient population. Although the laryngeal mask does not reliably protect against aspiration, we believe it may play a useful role if more conventional methods of airway management fail. Further studies in the trauma scenario are indicated.

Use of percutaneous electrical nerve stimulation (PENS) in the short-term management of headache

Objective.–To evaluate the short‐term effects of percutaneous electrical nerve stimulation (PENS) in the management of three types of chronic headache.